Ioannis Bellos1, Georgios Daskalakis2, Vasilios Pergialiotis1. 1. Laboratory of Experimental Surgery and Surgical Research "N. S. Christeas", Athens University Medical School, National and Kapodistrian University of Athens, Athens, Greece. 2. First Department of Obstetrics and Gynecology, Alexandra Hospital, National and Kapodistrian University of Athens, Athens, Greece.
Abstract
OBJECTIVES: Nephrotoxicity represents a major complication of vancomycin administration, leading to high rates of morbidity and treatment failure. The aim of this meta-analysis was to evaluate the association between trough levels and risk of renal impairment, by defining an exposure-toxicity relationship and assessing its accuracy in predicting the development of acute kidney injury (AKI). METHODS: Medline, Scopus, CENTRAL, Clinicaltrials.gov and Google Scholar databases were systematically searched from inception. Studies examining the effects of trough levels on nephrotoxicity risk in adult patients were deemed eligible. RESULTS: The meta-analysis was based on 60 studies, including 13 304 patients. The development of AKI was significantly linked to both higher initial [standardized mean difference (SMD): 0.82; 95% CI: 0.65-0.98] and maximum (SMD: 1.06; 95% CI: 0.82-1.29) trough levels. Dose-response analysis indicated a curvilinear relationship between trough levels and nephrotoxicity risk (χ2 = 127.1; P value < 0.0001). A cut-off of 15 mg/L detected AKI with a sensitivity of 62.6% (95% CI: 55.6-69.2) and a specificity of 65.5% (95% CI: 58.9-71.6), while applying a 20 mg/L threshold resulted in a sensitivity of 42.9% (95% CI: 34-52.2) and a specificity of 82.5% (95% CI: 73.9-88.8). CONCLUSIONS: The present findings suggest that the development of vancomycin-induced AKI is significantly associated with higher initial and maximum trough levels. An exposure-response relationship was defined, indicating that increasing trough levels correlate with a significant rise of nephrotoxicity risk. Future studies should verify the effectiveness of individualized pharmacokinetic tools that would enable the attainment of trough level targets and minimize the risk of renal toxicity.
OBJECTIVES:Nephrotoxicity represents a major complication of vancomycin administration, leading to high rates of morbidity and treatment failure. The aim of this meta-analysis was to evaluate the association between trough levels and risk of renal impairment, by defining an exposure-toxicity relationship and assessing its accuracy in predicting the development of acute kidney injury (AKI). METHODS: Medline, Scopus, CENTRAL, Clinicaltrials.gov and Google Scholar databases were systematically searched from inception. Studies examining the effects of trough levels on nephrotoxicity risk in adult patients were deemed eligible. RESULTS: The meta-analysis was based on 60 studies, including 13 304 patients. The development of AKI was significantly linked to both higher initial [standardized mean difference (SMD): 0.82; 95% CI: 0.65-0.98] and maximum (SMD: 1.06; 95% CI: 0.82-1.29) trough levels. Dose-response analysis indicated a curvilinear relationship between trough levels and nephrotoxicity risk (χ2 = 127.1; P value < 0.0001). A cut-off of 15 mg/L detected AKI with a sensitivity of 62.6% (95% CI: 55.6-69.2) and a specificity of 65.5% (95% CI: 58.9-71.6), while applying a 20 mg/L threshold resulted in a sensitivity of 42.9% (95% CI: 34-52.2) and a specificity of 82.5% (95% CI: 73.9-88.8). CONCLUSIONS: The present findings suggest that the development of vancomycin-induced AKI is significantly associated with higher initial and maximum trough levels. An exposure-response relationship was defined, indicating that increasing trough levels correlate with a significant rise of nephrotoxicity risk. Future studies should verify the effectiveness of individualized pharmacokinetic tools that would enable the attainment of trough level targets and minimize the risk of renal toxicity.
Authors: Nori J L Smeets; Esther M M Teunissen; Kim van der Velden; Maurice J P van der Burgh; Demi E Linders; Elodie Teesselink; Dirk-Jan A R Moes; Camilla Tøndel; Rob Ter Heine; Arno van Heijst; Michiel F Schreuder; Saskia N de Wildt Journal: Pediatr Nephrol Date: 2022-08-02 Impact factor: 3.651
Authors: Kate S Grattan; Mohamed Mohamed Ali; Seyed M Hosseini-Moghaddam; Hayley J I Gilmour; Gregory P Crunican; Erica Hua; Kelly A Muhsin; Rochelle Johnstone; Lise C Bondy; Megan K Devlin; Sarah Shalhoub; Sameer Elsayed; Michael S Silverman Journal: JAC Antimicrob Resist Date: 2021-01-18